The patents and publications referred to throughout the specification are incorporated herein by reference as if set forth verbatim.
The retina contains seven layers of alternating cells and processes that convert a light signal into a neural signal. The retinal photoreceptors and adjacent retinal pigment epithelium (RPE) form a functional unit that, in many disorders, becomes unbalanced due to genetic mutations or environmental conditions (including age). This results in loss of photoreceptors through apoptosis or secondary degeneration, which leads to progressive deterioration of vision and, in some instances, to blindness (for a review, see, e.g., Lund, R. D. et al. 2001, Progress in Retinal and Eye Research 20: 415-449). Two classes of ocular disorders that fall into this pattern are retinitis pigmentosa (RP) and age-related macular degeneration (AMD).
RP is mainly considered an inherited disease—over 100 mutations have been associated with photoreceptor loss (see Lund et al., 2001, supra). Though the majority of mutations target photoreceptors, some affect RPE cells directly. Together, these mutations affect such processes as molecular trafficking between photoreceptors and RPE cells and phototransduction, for example.
The primary disorder in AMD appears to be due to RPE dysfunction and changes in Bruch's membranes, e.g., lipid deposition, protein cross-linking and decreased permeability to nutrients (see Lund et al., 2001 supra). A variety of elements may contribute to macular degeneration, including genetic makeup, age, nutrition, smoking and exposure to sunlight.
Diabetic retinopathy, the leading cause of blindness in adults, results from abnormal circulation in the retina (National Eye Institute Website, www.nei.nih.gov; accessed Oct. 7, 2006). It begins with microaneurysms in the retina as areas of balloon-like swelling in the retina's tiny blood vessels are formed. These blood vessels become blocked depriving portions of the retina of a blood supply. This trauma causes the retina to secrete vascularization signals which result in new, abnormal blood vessels being formed. During this stage, known as proliferative diabetic retinopathy, the abnormal vessels proliferate along the retina and extend to the surface of the vitreous gel that fills the eye. The thin fragile walls of the abnormal vessels eventually leak blood into the vitreous gel causing vision loss and ultimately blindness. In the later phases of the disease, continued abnormal vessel growth and scar tissue may lead to further retinal degeneration including retinal detachment and glaucoma.
The two main treatments for diabetic retinopathy are photocoagulation and vitrectomy. Photocoagulation is a laser treatment that is used to treat advanced diabetic retinopathy (i.e. proliferative diabetic retinopathy). It involves the laser cauterization of the abnormal blood vessels that leak blood and other fluids into the vitreous gel of the eye. If there is a small amount of leakage, the laser is applied directly to specific points where the leaks occur (focal laser treatment). If the leakage is widespread or diffuse, laser burns are applied in a grid pattern over a broad area (grid laser treatment).
Panretinal photocoagulation is another laser-based treatment for diabetic retinopathy. According to this method, the entire retina (excluding the macula) is treated with scattered laser burns. This process causes the abnormal blood vessels to shrink thereby reducing the chances of hemorrhages in the vitreous gel.
Vitreoctomy provides another mode of treatment for diabetic retinopathy. A vitrectomy is a surgical procedure for correcting large blood vessel leaks in the vitreous gel. According to this procedure, the blood-filled vitreous is surgically removed from the eye. This hemorrhagic tissue is then replaced with a balanced salt solution to maintain the eye's shape and interocular pressure.
Photocoagulation and vitrectomies only offer a temporary solution to the vision loss caused by diabetic retinopathy. This is because these procedures only treat abnormal blood vessel formation as it occurs. They do not offer a lasting solution that addresses the cause of abnormal blood vessel formation which is compromised retinal circulation. As a result, photocoagulation and vitrectomies must be performed repeatedly in order to maintain long-term vision. Panretinal photocoagulation also has the undesirable side effect of causing the loss of peripheral vision and compromised night vision. A drawback of vitrectomy is that it requires a long recovery period during which the patient must remain facing the ground.
What is needed is a diabetic retinopathy treatment that prevents the abnormal blood vessel formation that leads to lost vision.